The lipids of red cell and platelet membranes are not fixed in amount. Rather, they are dependent in part on the lipid composition of their plasma environment. While certain features of this dependency are known, much is still unexplained. Over the past several years, our laboratory has been interested in factors which influence the lipid composition of red cells and platelets, particularly in human disease. One effect of changes in membrane lipid composition is a change in the fluidity of the hydrophobic portion of membrane. Membrane fluidity is strongly influenced by the amount of cholesterol relative to phospholipid in membranes. We have shown that the increased cholesterol/phospholipid of human red cells is strongly associated with an increase in the cholesterol/phospholipid of plasma lipoproteins in liver disease. We have also shown that there is a disproportionate increase in cholesterol in both the platelets and low density lipoproteins of patients with type II hyperlipoproteinemia. Abnormalities of membrane function exist in both of these diseases. We propose to explore the factors which lead to lipid transfer from lipoproteins to red cell and platelet membranes, to assess the effect of changes in lipid composition on the fluidity of platelet and red cell membranes and to relate the lipid composition and fluidity of these cell membranes to the functions of red cells and platelets.